Expression and regulation of CCL15 by human airway smooth muscle cells

P. Joubert, S. Lajoie-Kadoch, V. Wellemans, S. Létuvé, M. K. Tulic, A. J. Halayko, Q. Hamid

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Structural cells are an important reservoir of chemokines that coordinate the influx of various immune cells to the lungs of asthmatics. Airway smooth muscle cells (ASMC) are an important source of these chemokines. CCL15 is a recently described chemo-attractant for neutrophils, eosinophils, monocytes and lymphocytes. Objective: To determine the production and the regulation of CCL15 by ASMC and to investigate its production in asthmatic airways. Methods: Human ASMC were obtained from main bronchial airway segments of patients with mild, moderate and severe asthma. To induce chemokine production, cells were incubated with IL-4, IL-13, TNF-α or IFN-γ in presence or absence of dexamethasone, mithramycin A (SP-1 inhibitor) or the IKK-2 inhibitor, AS602868. CCL15 mRNA expression was evaluated by real-time PCR. Immunoreactive CCL15 was detected by immuno-fluorescence and CCL15 protein concentration in the supernatant was measured using ELISA. Results: CCL15 is constitutively expressed in human ASMC and is strongly up-regulated by TNF-α. This up-regulation is inhibited by dexamethasone, mithramycin A and AS602868. TNF-α-induced CCL15 levels can be synergistically enhanced by the presence of IFN-γ, at both the transcriptional and translation level. This synergism is NF-κB-dependent. Asthmatic biopsies demonstrated higher expression of CCL15 compared with non-asthmatic controls. Conclusion and Clinical Relevance: Our results show that ASMC are a potent source of CCL15 in the airways and may directly participate in the recruitment of inflammatory cells to asthmatic airways. Targeting the production of CCL15 by ASMC might reduce the inflammatory response within the airways of asthmatic patients.

Original languageEnglish (US)
Pages (from-to)85-94
Number of pages10
JournalClinical and Experimental Allergy
Volume42
Issue number1
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

Keywords

  • Airway smooth muscle cells
  • Asthma
  • Chemokine
  • Cytokines
  • Leukotactin-1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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